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Choline is required to make essential membrane phospholipids. It is a precursor for the biosynthesis of the neurotransmitter acetylcholine and also is an important source of labile methyl groups. Mammals fed a choline-deficient diet develop liver dysfunction; however, choline is not considered an essential nutrient in humans. Healthy male volunteers were hospitalized and fed a semisynthetic diet devoid of choline supplemented with 500 mg/day choline for 1 wk. Subjects were randomly divided into two groups, one that continued to receive choline (control), and the other that received no choline (deficient) for three additional wk. During the 5th wk of the study all subjects received choline. The semisynthetic diet contained adequate, but no excess, methionine. In the choline-deficient group, plasma choline and phosphatidylcholine concentrations decreased an average of 30% during the 3-wk period when a choline-deficient diet was ingested; plasma and erthrocyte phosphatidylcholine decreased 15%; no such changes occurred in the control group. In the choline-deficient group, serum alanine aminotransferase activity increased steadily from a mean of 0.42 mukat/liter to a mean of 0.62 mukat/liter during the 3-wk period when a choline-deficient diet was ingested; no such change occurred in the control group. Other tests of liver and renal function were unchanged in both groups during the study. Serum cholesterol decreased an average of 15% in the deficient group and did not change in the control group. Healthy humans consuming a choline-deficient diet for 3 wk had depleted stores of choline in tissues and developed signs of incipient liver dysfunction. Our observations support the conclusion and choline is an essential nutrient for humans when excess methionine and folate are not available in the diet.

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Overweight and obesity are important risk factors for type 2 diabetes. The marked increase in the prevalence of overweight and obesity is presumably responsible for the recent increase in the prevalence of type 2 diabetes. Lifestyle modification aimed at reducing energy intake and increasing physical activity is the principal therapy for overweight and obese patients with type 2 diabetes. Even moderate weight loss in combination with increased activity can improve insulin sensitivity and glycemic control in patients with type 2 diabetes and prevent the development of type 2 diabetes in high-risk persons (ie, those with impaired glucose tolerance). The American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition have joined together to issue this statement on the use of lifestyle modification in the prevention and management of type 2 diabetes.

Choline is a precursor for the biosynthesis of phosphatidylcholine (lecithin), sphingomyelin, and choline plasmalogens--all essential constituents of membranes. Choline is also needed to make acetylcholine, a major neurotransmitter. The major choline-containing compounds of human milk (unesterified choline, phosphatidylcholine, sphingomyelin) were measured in samples obtained from mothers of full-term infants. Unesterified choline concentrations were highest (greater than 600 nmol/ml) during the first week of lactation, but thereafter remained relatively constant at 70-200 nmol/ml. There was no difference among foremilk, middle milk and hind milk, nor was there a diurnal pattern of variation in unesterified choline concentrations. Milk phosphatidylcholine and sphingomyelin concentrations remained relatively constant throughout lactation (100-200 nmol/ml). Hind milk always contained more of these phospholipids than did foremilk or middle milk. There was no consistent diurnal pattern of variation in milk concentrations of phosphatidylcholine or sphingomyelin. Milk contained no phospholipase activity capable of forming free choline from phosphatidylcholine or sphingomyelin. Bovine milk contained approximately the same concentrations of choline, phosphatidylcholine and sphingomyelin as did human milk from mothers more than 15 d postpartum. The same was true of "humanized" infant formulas made from cow's milk. Soy protein-based formulas had much more unesterified choline (up to 650 nmol/ml) and much less sphingomyelin than did mature human milk.

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Choline is an essential nutrient for some mammals; it is used for membrane and neurotransmitter synthesis. We analyzed plasma samples, obtained periodically during TPN therapy, for choline concentration. Malnourished patients referred to a nutrition support service were prospectively assigned to be treated with daily infusions of amino acids with, and without, supplemental daily infusions of lipid emulsion for a period of 1 wk. After the first week, all subjects received intravenous lipid, and most were offered enteral food supplements. Initial plasma choline concentrations in the 25 malnourished patients were significantly lower than those measured in plasma samples from 23 hospitalized patients known to be eating well (6.5 +/- 0.6 vs 9.7 +/- 0.7 nmol/ml; mean +/- SEM; p less than 0.001). During the first week of TPN therapy, plasma choline concentrations in the lipid-restricted group tended to decrease (from 7.3 +/- 1.0 to 4.7 +/- 0.5 nmol/ml; mean +/- SEM; p less than 0.05), while in the lipid-supplemented group plasma choline tended to increase (from 5.6 +/- 0.5 to 6.2 +/- 0.7 nmol/ml; mean +/- SEM; p less than 0.05). Plasma choline concentration increased during wk 2-4, when all patients were treated with lipid emulsions, and some were offered enteral foods. We conclude that malnourished humans who eat no choline have diminished stores of plasma (and possibly tissue) choline.

MATERIALS AND METHODSthe developing small intestine are frequently different from those characterized in the intestine of mature animals (9-13).In the present studies, we examined the kinetics of choline uptake in the developing small intestine and compared these transport characteristics with those found in the intestine of mature animals.Animals. Adult, male Sprague-Dawley rats (Charles River Breeding Laboratory, Wilmington, MA), each weighing 100-125 g, were housed in stainless steel cages. Rat Chow (Ralston Purina, St. Louis, MO; 0.16% unesterified choline by our assay) and water were given ad libitum for 1 wk prior to use in our studies. Temperature in the housing facility was 24°C. The light cycle was 12 h long, 0600 to 1800 h.Neonatal animals used in these studies were kept with lactating dams up to the time of the experiment. Litter size was limited to 10 pups per dam. Mothers were fed rat Chow (Ralston Purina; 0.16% unesterified choline by our assay) and water ad libitum. Rat milk contained 100-300 ILM unesterified choline by our assay. Only male rat pups, 10-11 days old, were used in the experiments described. Measurement o/uptake by gut slices. Adult rats were anesthetized with ether, a midline abdominal incision was made, and the small intestine was visualized. Segments taken from the area immediately distal to the end of the stomach were designated as duodenum. Jejunal segments were taken from the area whose blood supply was derived from the jejunal artery. Ileal segments were taken from the area 10 cm proximal to the cecum. Colonic segments were taken from the area immediately distal to the cecum. In the 10-day-old rat, segments ofjejunum were collected from the small intestine from the area whose blood supply was derived from the jejunal artery.Gut sections were removed and placed in ice-cold KRB containing 10 mM glucose. They were cut longitudinally, rinsed with KRB, and trimmed to a length of 2 cm. These tissue slices were supported on filter paper (Whatman no. 3) and placed in a prewarmed (3r C), modified~Ussing chamber containing KRB in the bottom portion of the chamber (11,18). The top of the chamber was positioned over the gut slice and clamped down. KRB containing choline, 14C-choline, 3H-inulin, and nonradiolabeled inulin (or 3H-D-glucose and D-glucose) was added to this upper chamber. A gas containing 95% oxygen and 5% carbon dioxide was bubbled through the medium throughout the 15-min incubatinn period. 768 Abbreviations KRB, Krebs' Ringer buffer containing 10 mM glucose TLC, thin-layer chromatography